Exotic species have demonstrated their utility as models for the study of a wide range of hereditary and infectious diseases and physical traits. However, to fully interpret the results of these studies, it is necessary to understand their evolutionary history. This involves not only a more precise description of the phylogenetic relationships among species, but also an assessment of the uniqueness among wild populations and knowledge of historic patterns of gene flow. Our primary animal model has been the domestic cat and their exotic relatives and wild populations. As a crucial step in this process, we have developed the foremost collection of biological samples from captive and wild populations of cats, which has provided the theoretical and conceptual framework for our research. The recently-released whole genome sequence of the domestic cat has provided an important tool for our research and is greatly accelerating the pace of gene discovery and comparative genomic inference. The recently completed description of the evolution of the cat family will also facilitate more detailed study of selection and gene evolution among felid species and populations. Our comparative genomic studies are expanding to include the primate, camelid, and pangolin families. We have completed development of an RH map of the alpaca which will facilitate the study of candidate genes for inherited diseases in camelids and related ungulate species, including several related to human disorders. We are currently annotating the 8X WGS of the alpaca. Study of the pangolin, a group of species distributed in Africa and Asia and the closest relatives to carnivores, will provide good models for comparative genomic studies among these increasingly well-studied groups. A comprehensive phylogeny, linked with precise estimates of when and where different groups diverged will greatly enhance our ability to interpret human genetic variation in the context of human evolutionary history. Our research on primates, camelids, pangolins will be increasingly important given the inclusion of both the alpaca and the pangolin on the short list of species for low-coverage, whole-genome-sequencing. The potential of the alpaca (Lama glama) animal model was elevated with its selection by NHGRI in 2008 as one of a small number of species to be sequenced at high density (10x) using the newest generation of ROCHE 454 Titanium sequencing methodologies (Sequencing was completed in Spring 2009). The alpaca sequencing project had been initially funded by National Human Genome Research Institute (NHGRI) for 2x WGS coverage because of the alpacas divergent position of the camelid lineage at the base of the diverse Cetartiodactyla order. Artiodactyla also contains the majority of domesticated mammal species, including cattle, pigs, goats, sheep, reindeer, and four camelid species: the Dromedary camel (Camelus dromedarius) of northern Africa and south-west Asia, the Bactrian camel (Camelus bactrianus) of eastern Asia and the South American (new world) camels, and the llama (Lama pacos) and alpaca (Lama glama). The alpaca study offers unusual comparative opportunities for homologous human disease (186). Over 80 congenital defects are identified among candid species, nearly half with human homology. In addition, alpacas have a unique immune system, which includes Y-shaped antibody molecules consisting of unique heavy-chain only antibodies, which makes them smaller and more durable. These display are remarkable therapeutic anti-viral and anti-bacterial properties of camel milk, including, elevated Vitamin C content, an insulin-like protein that reduces medication needed by diabetics, and assistance in the control of high blood pressure and management of arteriosclerosis and osteoporosis. Camelid species have also developed unique ecological adaptations to a life in harsh, near-waterless environments. Thriving in challenging habitats in the developing world, these robust efficient animals provide income, food, and fertilizer and help sustain the communitys health and environment. We have a growing collection of biological tissues and developing pedigrees afflicted with malignancies, polydactyly, blue eye deafness, short ears, curved limbs, dwarfishness, and syndactyly.